A 45-year-old right-handed teacher presents with a 3-month history of progressive right-sided weakness and new-onset seizures. His wife reports subtle personality changes over the past 6 weeks. On examination: GCS 15, mild right arm weakness (4/5), brisk right-sided reflexes, and right plantar extensor response.
MRI brain: A 4cm ring-enhancing lesion in the left frontal lobe with surrounding oedema and 8mm midline shift.
What is your differential diagnosis? How would you approach this patient?
Classification of Brain Tumours
Brain tumours are classified as either primary (arising from brain tissue itself) or secondary/metastatic (spread from elsewhere). This distinction is fundamental — metastases are actually the most common brain tumours overall, outnumbering primary tumours 10:1.
| Type | Origin | Common Examples | Frequency |
|---|---|---|---|
| Primary — Glial | Glial cells (astrocytes, oligodendrocytes) | Glioblastoma, Astrocytoma, Oligodendroglioma | ~30% of primary tumours |
| Primary — Non-glial | Meninges, nerve sheaths, pituitary | Meningioma, Schwannoma, Pituitary adenoma | ~40% of primary tumours |
| Metastatic | Lung, breast, melanoma, renal, colorectal | Multiple ring-enhancing lesions | Most common overall |
| Paediatric | Posterior fossa predominant | Medulloblastoma, Ependymoma, Pilocytic astrocytoma | Most common solid tumour in children |
WHO Grading System
The WHO classifies brain tumours from Grade 1 to Grade 4 based on histological features and molecular markers. Higher grade = more aggressive = worse prognosis.
| WHO Grade | Features | Example | Median Survival |
|---|---|---|---|
| Grade 1 | Slow growing, well-differentiated, potentially curable with surgery | Pilocytic astrocytoma | >10 years |
| Grade 2 | Slow growing but infiltrative, tendency to progress | Diffuse astrocytoma | 5–10 years |
| Grade 3 | Anaplastic, mitotic activity, aggressive | Anaplastic astrocytoma | 2–5 years |
| Grade 4 | Highly malignant, necrosis, microvascular proliferation | Glioblastoma (GBM) | 12–15 months |
Glioblastoma Multiforme (GBM) is the most common and most aggressive primary brain tumour in adults. It is characterised by the "butterfly glioma" pattern crossing the corpus callosum on MRI, and a ring-enhancing lesion with central necrosis. Despite surgery, radiotherapy and temozolomide chemotherapy, median survival remains only 12–15 months.
Clinical Presentation
Brain tumours present through three main mechanisms — raised ICP, focal neurological deficits, and seizures. The pattern depends on tumour location and speed of growth.
Presenting Features by Mechanism
- Raised ICP: Morning headache (worse on waking), nausea/vomiting, papilloedema, deteriorating consciousness. Caused by mass effect and surrounding oedema.
- Focal deficits: Depend entirely on location — frontal (personality change, weakness), temporal (speech, memory), parietal (sensory, neglect), occipital (visual field defects), cerebellum (ataxia, dysarthria).
- Seizures: New-onset seizures in an adult over 40 must be investigated for a structural cause. Focal seizures with secondary generalisation are typical of cortical tumours.
- Subacute progression: Unlike stroke (sudden), tumours cause gradually worsening deficits over weeks to months — this history is crucial.
Investigations
MRI with gadolinium contrast is the gold standard — it shows tumour location, size, enhancement pattern, oedema, and midline shift. CT head is done urgently if MRI is unavailable or the patient is too unstable.
Key MRI features to know: ring enhancement = high grade glioma or metastasis; homogeneous enhancement = meningioma or low-grade glioma; multiple lesions = metastases until proven otherwise.
Tissue diagnosis is essential — MRI alone cannot distinguish tumour types reliably. Options include stereotactic biopsy (for deep/eloquent area tumours) or surgical resection with intraoperative frozen section.
Principles of Management
Management Framework
- Dexamethasone: Reduces perilesional oedema rapidly — 4–8mg IV/oral. Start immediately in symptomatic patients. Does not treat the tumour but can dramatically improve neurological function within 24–48 hours.
- Antiepileptics: For patients who have had seizures. Levetiracetam is preferred — fewer drug interactions than phenytoin, important when chemotherapy is planned.
- Surgery: Aims for maximal safe resection while preserving function. Extent of resection correlates with survival in high-grade gliomas. Intraoperative tools include awake craniotomy, fluorescence-guided surgery (5-ALA), and neuronavigation.
- Radiotherapy: Standard adjuvant treatment for high-grade gliomas. Whole brain radiotherapy for multiple metastases; stereotactic radiosurgery (Gamma Knife) for 1–3 metastases.
- Chemotherapy: Temozolomide is standard for GBM (Stupp protocol). MGMT promoter methylation predicts response — test all GBM specimens.
- Palliative care: For Grade 4 tumours, early palliative involvement improves quality of life and may extend survival.
The ring-enhancing lesion with surrounding oedema in a 45-year-old with progressive deficits and seizures is GBM until proven otherwise. He was started on dexamethasone 8mg BD and levetiracetam. MR spectroscopy supported high-grade glioma. He underwent left frontal craniotomy with fluorescence-guided resection. Histology confirmed GBM, MGMT unmethylated. He received Stupp protocol (temozolomide + radiotherapy). Median survival in this group is 12 months — he and his family were counselled honestly with early palliative involvement.
Metastases are more common than primary brain tumours. WHO Grade 1–4 guides prognosis and treatment. New seizures in adults over 40 need structural imaging. Ring enhancement = high-grade glioma or metastasis. Start dexamethasone early. Tissue diagnosis is mandatory. GBM = surgery + temozolomide + radiotherapy, median survival 12–15 months.
References
- Louis DN et al. The 2021 WHO Classification of Tumors of the Central Nervous System. Neuro-Oncology. 2021;23(8):1231–1251.
- Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM. 2005;352(10):987–996.
- Weller M et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nature Reviews Clinical Oncology. 2021;18:170–186.
